We evaluated whether indications for liver transplantation (LT) have changed among people with/without human immunodeficiency virus (HIV) infection and compared LT outcomes and trends by HIV serostatus. LT recipients (2008-2018) from the United Network for Organ Sharing and Organ Procurement and Transplantation Network (UNOS/OPTN) were identifed. Among 62 195 LT recipients, 352 (0.6%) were HIV-infected. The proportion of HIV-infected patients increased over time (P trend = .001), as did the number of transplant centers performing LT for HIV-infected recipients; average annual percentage change of 9.2% (p < .001). Nonviral causes became the leading indication in 2015 for HIV-uninfected and in 2018 for HIV-infected (P trend < .001). Three-year cumulative patient survival rates were 77.5%, for HIV-infected and 84.6%, for HIV-uninfected (p = .15). Over time, graft and patient survival rates improved for both HIV-infected and uninfected (p < .001). Among HCV-infected LT recipients, 3-year patient survival rates were 72.5% for HIV-infected and 81.8% for HIV-uninfected (p = .02). However, in a subanalysis restricted to 2014-2018, differences in graft and patient survival by HIV serostatus were no longer observed (3-year patient survival rates were 81.2% for HIV-infected and 86.4% for HIV-uninfected, p = .34). In conclusion, in the United States, nonviral liver disease is now the leading indication for LT in HIV-infected patients, and posttransplant outcomes have improved over time.

We evaluated trends and outcomes of liver transplantation (LT) recipients with/without HIV infection.

LT recipients between 2008 and 2015 from the United Network for Organ Sharing and Organ Procurement and Transplantation Network and European Liver Transplant Registry were included. Trends and characteristics related to survival among LT recipients with HIV infection were determined.

Among 73 206 LT patients, 658 (0.9%) were HIV-infected. The proportion of LT HIV-infected did not change over time (P-trend = 0.16). Hepatitis C virus (HCV) as indication for LT decreased significantly for HIV-infected and HIV-uninfected patients (P-trends = 0.008 and <0.001). Three-year cumulative graft survival in LT recipients with and without HIV infection was 64.4% and 77.3%, respectively (P < 0.001), with improvements over time for both, but with HIV-infected patients having greater improvements (P-trends = 0.02 and 0.03). Adjusted risk of graft loss was 41% higher in HIV-infected versus HIV-uninfected (adjusted hazard ratio [aHR], 1.41; P < 0.001). Among HIV-infected, model of end-stage liver disease (aHR, 1.04; P < 0.001), body mass index <21 kg/m (aHR, 1.61; P = 0.006), and HCV (aHR, 1.83; P < 0.001) were associated with graft loss, whereas more recent period of LT 2012-2015 (aHR, 0.58; P = 0.001) and donor with anoxic cause of death (aHR, 0.51; P = 0.007) were associated with lower risk of graft loss.

Patients with HIV infection account for only 1% of LTs in United States and Europe, with fewer LT for HCV disease over time. A static rate of LT among HIV-infected patients may reflect improvements in cirrhosis management and/or persistent barriers to LT. Graft and patient survival among HIV-infected LT recipients have shown improvement over time.

Human immunodeficiency virus (HIV) infection was considered a contraindication for solid organ transplantation (SOT) in the past. However, HIV management has improved since highly active antiretroviral therapy (HAART) became available in 1996, and the long-term survival of patients living with HIV has led many transplant programs to reevaluate their policies regarding the exclusion of patients with HIV infection.Based on the available data in the medical literature and the cumulative experience of transplantation in HIV-positive patients at our hospital, the aim of the present article is to outline the criteria for transplantation in HIV-positive patients as recommended by the Immunocompromised Host Committee of the Hospital das Clínicas of the University of São Paulo.

Direct-acting antivirals have proved to be highly efficacious and safe in monoinfected liver transplant (LT) recipients who experience recurrence of hepatitis C virus (HCV) infection. However, there is a lack of data on effectiveness and tolerability of these regimens in HCV/HIV-coinfected patients who experience recurrence of HCV infection after LT. In this prospective, multicenter cohort study, the outcomes of 47 HCV/HIV-coinfected LT patients who received DAA therapy (with or without ribavirin [RBV]) were compared with those of a matched cohort of 148 HCV-monoinfected LT recipients who received similar treatment. Baseline characteristics were similar in both groups. HCV/HIV-coinfected patients had a median (IQR) CD4 T-cell count of 366 (256-467) cells/µL. HIV-RNA was <50 copies/mL in 96% of patients. The DAA regimens administered were SOF + LDV ± RBV (34%), SOF + SMV ± RBV (31%), SOF + DCV ± RBV (27%), SMV + DCV ± RBV (5%), and 3D (3%), with no differences between the groups. Treatment was well tolerated in both groups. Rates of SVR (negative serum HCV-RNA at 12 weeks after the end of treatment) were high and similar for coinfected and monoinfected patients (95% and 94%, respectively; P = .239). Albeit not significant, a trend toward lower SVR rates among patients with advanced fibrosis (P = .093) and genotype 4 (P = .088) was observed. In conclusion, interferon-free regimens with DAAs for post-LT recurrence of HCV infection in HIV-infected individuals were highly effective and well tolerated, with results comparable to those of HCV-monoinfected patients.

 Background and aims. Pegylated interferon (Peg-INF) and ribavirin (RBV) based therapy is suboptimal and poorly tolerated. We evaluated the safety, tolerability and efficacy of a 24-week course of sofosbuvir plus daclatasvir without ribavirin for the treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LT) in both HCV-monoinfected and human immunodeficiency virus (HIV)-HCV coinfected patients.

We retrospectively evaluated 22 consecutive adult LT recipients (16 monoinfected and 6 coinfected with HIV) who received a 24-week course of sofosbuvir plus daclatasvir treatment under an international compassionate access program.

Most patients were male (86%), with a median age of 58 years (r:58-81y). Median time from LT to treatment onset was 70 months (r: 20-116 m). HCV genotype 1b was the most frequent (45%), 55% had not responded to previous treatment with Peg-INF and RBV and 14% to regiments including first generation protease inhibitors. Fifty-six percent of the patients had histologically proven cirrhosis and 6 had ascites at baseline. All patients completed the 24-week treatment course without significant side effects except for one episode of severe bradicardya, with only minor adjustments in immunosuppressive treatment in some cases. Viral suppression was very rapid with undetectable HCV-RNA in all patients at 12 weeks. All 22 patients achieved a sustained virological response 12 weeks after treatment completion.

The combination of sofosbuvir plus daclatasvir without ribavirin is a safe and effective treatment of HCV recurrence after LT in both monoinfected and HIV-coinfected patients, including those with decompensated cirrhosis.

IFN-based therapy against hepatitis C recurrence after liver transplantation (LT) has poor effectiveness and tolerability. In HIV/HCV-coinfected liver transplant recipients, the results are even poorer. Here, we report our experience using direct antiviral agents (DAAs) in 11 consecutive coinfected patients within the LT setting.

Four patients with compensated cirrhosis and hepatocellular carcinoma were treated while awaiting LT and seven patients received antiviral therapy due to severe hepatitis C recurrence after LT [fibrosing cholestatic hepatitis (n = 1), fibrosis stage ≥F3 (n = 2) and decompensated cirrhosis (n = 4)]. Patients were treated with different sofosbuvir-based regimens with or without ribavirin for 12 or 24 weeks.

Sustained virological response (SVR) was achieved in all patients. Two of the four patients treated while awaiting LT reached the time of transplant with undetectable HCV-RNA that remained undetectable 12 weeks after LT, one patient had detectable HCV-RNA at the time of transplant but achieved SVR after completing 12 weeks of therapy after LT and the last patient is still on the waiting list. Seven patients with severe post-LT hepatitis C recurrence were treated within 11-120 months after LT. In these patients, viral eradication was associated with an improvement in liver function and clinical decompensation. Tolerance to antiviral therapy was good and only four patients reported mild adverse events.

IFN-free regimens are effective and well tolerated in HIV/HCV-coinfected patients within the LT setting, but more data are needed to confirm our promising results and to establish the best treatment option in this population.

Antiviral treatment in liver transplant recipients co-infected with hepatitis C virus (HCV) and HIV remains a challenge. We herein report a case of HCV recurrence that was successfully treated using interferon-free anti-HCV therapy with daclatasvir and asunaprevir. A 48-year-old man underwent antiviral therapy with a 24-week course of daclatasvir and asunaprevir for biopsy-proven recurrent HCV 15 months after living donor liver transplantation, following non-response to pre-emptive antiviral treatment with pegylated interferon plus ribavirin. Anti-HIV and immunosuppressive regimens were modified safely. Renal function was feasibly preserved. The anti-HCV effect was remarkable with an undetectable viral load confirmed within 2 weeks, and this patient achieved a sustained virological response after 12 weeks of post-transplantation treatment. No serious adverse events were observed. This case indicates that daclatasvir and asunaprevir for recurrent HCV in a HIV co-infected recipient after liver transplantation is safe and effective.

For liver transplant recipients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection, recurrence after LT is associated with a higher risk of graft loss than for HCV mono-infected patients. Prior HCV treatment options were limited by side effects and drug-drug interactions.

To evaluate treatment outcomes with sofosbuvir (SOF)-based therapy among HIV/HCV coinfected liver transplant recipients.

Access to SOF and ribavirin (RBV) prior to regulatory approval was attained via an international compassionate access program for transplant recipients with a life expectancy of 1 year or less in the absence of HCV treatment. This report focuses on the short and longer term outcomes in HCV-HIV co-infected liver transplant recipients.

Twenty patients were treated, nine with early severe recurrence and 11 with cirrhosis. Eleven patients received SOF and RBV, one SOF, RBV and Peg-interferon, three SOF, RBV and simeprevir and five SOF, RBV and daclatasvir. Of the 18 patients who completed treatment, 16 (89%) achieved sustained virological response 12 weeks after the end of treatment (SVR12). Liver function tests (including bilirubin and albumin) improved significantly over time. Nineteen serious adverse events occurred in eight (40%) patients, none of them related to SOF. Two patients died during treatment and another, 1 year after the end of therapy, due to progressive end-stage liver disease. Importantly, HIV suppression was not compromised. No significant drug-drug interactions were reported.

Sofosbuvir-based regimens are safe, well-tolerated and provide high rates of SVR in HCV-HIV co-infected patients with severe recurrence after-liver transplant.

India contributes significantly to the global burden of HCV. While the nucleoside NS5B inhibitor sofosbuvir became available in the Indian market in March 2015, the other directly acting agents (DAAs), Ledipasvir and Daclatasvir, have only recently become available in the India. The introduction of these DAA in India at a relatively affordable price has led to great optimism about prospects of cure for these patients as not only will they provide higher efficacy, but combination DAAs as all-oral regimen will result in lower side effects than were seen with pegylated interferon alfa and ribavirin therapy. Availability of these newer DAAs has necessitated revision of INASL guidelines for the treatment of HCV published in 2015. Current considerations for the treatment of HCV in India include the poorer response of genotype 3, nonavailability of many of the DAAs recommended by other guidelines and the cost of therapy. The availability of combination DAA therapy has simplified therapy of HCV with decreased reliance of evaluation for monitoring viral kinetics or drug related side effects.

Recurrent hepatitis C virus (HCV) infection contributes to unfavourable outcomes in HIV/HCV coinfected liver transplant recipients. Direct-acting antiviral (DAA) therapies for HCV offer an opportunity to improve patient and allograft survival in this patient population. We evaluated treatment outcomes with sofosbuvir (SOF)-based DAA therapy among HIV/HCV coinfected liver transplant recipients.

Single centre prospective cohort study.

We identified eight HIV/HCV coinfected liver transplant recipients who were prospectively followed in the Northwestern University Viral Hepatitis Registry and who received SOF-based DAA therapy. We evaluated responses to therapy, including sustained HCV viral response 12 weeks after therapy completion (SVR12) and adverse effects.

Seven recipients (87.5%) completed 12 weeks of SOF-based therapy: SOF/simeprevir for genotype 1 (n = 6), SOF/ribavirin for genotype 2 (n = 1). Of persons who completed therapy, all achieved SVR12. Strategies for the management of expected and observed drug interactions consequent to the addition of simeprevir to preexisting complex medication regimens included modifications of HIV antiretroviral regimens (n = 4) and tacrolimus dosing (n = 4) and frequent monitoring of tacrolimus trough levels. Minor adverse effects were observed after DAA initiation. One episode of allograft rejection and one death occurred that were deemed unlikely related to HCV therapy.

High rates of HCV treatment success and no treatment-limiting adverse effects were observed in this HIV/HCV liver transplant cohort. Complex drug interactions were successfully managed in the context of multidisciplinary specialty care. Further studies are needed to assess the long-term effects of DAA therapy on patient and allograft survival among HIV/HCV coinfected liver transplant recipients.

To review the experience to date and unique challenges associated with liver transplantation in hepatitis C virus (HCV)/HIV-coinfected patients.

The prevalence of cirrhosis and hepatocellular carcinoma is rising among HIV-infected individuals. With careful patient selection and in the absence of HCV infection, HIV-infected and HIV-uninfected liver transplant recipients have comparable posttransplant outcomes. However, in the presence of HCV infection, patient and graft survival are significantly poorer in HIV-infected recipients, who have a higher risk of aggressive HCV recurrence, acute rejection, sepsis, and multiorgan failure. Outcomes may be improved with careful recipient and donor selection and with the availability of new highly potent all-oral HCV direct acting antivirals (DAAs). Although all-oral DAAs have not been evaluated in HIV/HCV-coinfected transplant patients, HIV does not adversely impact treatment success in nontransplant populations. Therefore, there is great hope that HCV can be successful eradicated in HIV/HCV-coinfected transplant patients and will result in improved outcomes. Careful attention to drug-drug interactions with HIV antiretroviral agents, DAAs, and posttransplant immunosuppressants is required.

Liver transplant outcomes are poorer in HIV/HCV-coinfected recipients compared with those with HCV-monoinfection. The new HCV DAAs offer tremendous potential to improve outcomes in this challenging population.

In an era of great achievements in liver transplantation, hepatitis C viral infection (HCV) remains an unsolved problem. As a leading indication for liver transplantation in Western countries, HCV poses a significant burden both before and after transplantation. Post-transplant disease recurrence occurs in nearly all patients with detectable pretransplant viremia, compromising the lifesaving significance of transplantation. Many factors involving the donor, recipient and virus have been evaluated throughout the literature, although few have been fully elucidated and implemented in actual clinical practice. Antiviral therapy has been recognized as a cornerstone of HCV infection control; however, experience and success are diminished following transplantation in a challenging cohort of patients with liver cirrhosis. Current therapeutic protocols surpass those used previously, both in sustained viral response and side-effect profile. In this article we review the most relevant and contemporary scientific evidence regarding hepatitis C infection and liver transplantation, with special attention dedicated to novel, more efficient and safer antiviral regimens.